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TY - JOUR AU - Chen, Jia-Yang AU - Clifford, John AU - Zusi, Chris AU - Starrett, John AU - Tortolani, David AU - Ostrowski, Jacek AU - Reczek, Peter R. AU - Chambon, Pierre AU - Gronemeyer, Hinrich PY - 1996 DA - 1996/08/01 TI - Two distinct actions of retinoid-receptor ligands JO - Nature SP - 819 EP - 822 VL - 382 IS - 6594 AB - SIGNALLING by all-trans retinoic acid is mediated through RXR-RAR retinoid receptor heterodimers1,2, in which RXR has been considered to act as a transcriptionally silent partner3–5. However, we show here that in cultured NB4 (ref. 6) human acute promyelocytic leukaemia7–9 cells treated with either an RAR-α-selective agonist alone, or certain RAR-α antagonists in combination with an RXR agonist, receptor–DNA binding is induced in vivo, resulting in expression of the target genes of retinoic acid as well as acute promyelocytic leukaemia protein (PML) relocation to nuclear bodies10–12 and differentiation before apoptosis. These results indicate that RAR-α ligands can induce two separate events: one enables RXR–RAR-α heterodimers to bind to DNA in vivo and allows RXR agonists to act; the other induces transcriptional activity of RAR-α. The availability of receptor-specific synthetic retinoids that can induce distinct receptor functions has potential in extending the therapeutic repertoire of retinoids. SN - 1476-4687 UR - https://doi.org/10.1038/382819a0 DO - 10.1038/382819a0 ID - Chen1996 ER -